1. Field of the Invention
This invention relates to a new and improved process for the preparation of certain known anthracycline glycoside antibiotics. Also provided are novel intermediates useful in the above process.
2. Description of the Prior Art
Both the starting materials, daunomycin and its acid addition salts, and active end-products, C-4' etherified derivatives of adriamycin, prepared according to the present invention are known. Daunomycin (and its acid addition salts) is disclosed, for example, in U.S. Pat. No. 3,616,242. Adriamycin is disclosed in U.S. Pat. No. 3,590,028. The C-4' etherified derivatives of adriamycin produced by the process of the present invention are disclosed in U.K. patent application No. 2,002,754A and European patent application No. 14,853.
The halogenation of a daunomycin starting material to produce 14-halodaunomycin intermediates is disclosed in U.S. Pat. No. 3,803,124 as is the alkaline hydrolysis of these intermediates to give adriamycin. No suggestion of using the 14-halodaunomycin intermediate to produce C-4' etherified adriamycin derivatives is made in this reference.
U.S. Pat. No. 4,225,589 discloses bromination of daunomycin to give a 14-bromodaunomycin dimethylketal intermediate and the conversion of this ketal to a 14-bromodaunomycin by deketalisation with a ketone in the presence of hydrochloric acid. No disclosure is given, however, of the use of either of these intermediates to produce C-4' etherified adriamycin derivatives.